RESUMEN
BACKGROUND: Neurological manifestations are commonly reported in patients with celiac disease (CD). We aimed to characterize epilepsy features in a pediatric population with CD and the effect of a gluten-free diet (GFD) on seizure burden. METHODS: A retrospective chart review was performed on pediatric patients treated at the University of Utah and Primary Children's Hospital in Salt Lake City, Utah, with both epilepsy and CD and compared with a control group with epilepsy only. RESULTS: We identified 56 patients with epilepsy and biopsy-confirmed CD (n = 36, 64%) or elevated tissue transglutaminase antibodies (tTG-Ab) without biopsy-confirmed CD (n = 20, 36%). Age- and gender-matched controls were selected from patients with epilepsy only (n = 168). Patients with biopsy-proven CD or positive tTG-Ab had high percentage of drug-resistant epilepsy (DRE) compared with the control group (P < 0.05). Age at seizure onset preceded the diagnosis of CD on average by 5.9 years for patients with DRE (P < 0.01) compared with 2.2 years for those with drug-responsive epilepsy. Adhering to a GFD reduced seizure frequency or resulted in weaning dosage or weaning off of one or more antiseizure medications in a majority of patients with DRE. CONCLUSIONS: DRE was more prevalent in pediatric patients with biopsy-confirmed CD and positive tTG-Ab compared with the control group (which included childhood epilepsy syndromes), but comparable with the prevalence of DRE in the general population. Adherence to a GFD in combination with antiseizure medications appears to reduce seizure burden for those with CD and DRE.
Asunto(s)
Anticonvulsivantes/administración & dosificación , Enfermedad Celíaca , Dieta Sin Gluten , Epilepsia Refractaria , Síndromes Epilépticos , Adolescente , Enfermedad Celíaca/complicaciones , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Niño , Preescolar , Epilepsia Refractaria/dietoterapia , Epilepsia Refractaria/tratamiento farmacológico , Epilepsia Refractaria/etiología , Síndromes Epilépticos/dietoterapia , Síndromes Epilépticos/tratamiento farmacológico , Síndromes Epilépticos/etiología , Femenino , Humanos , Lactante , Masculino , Estudios RetrospectivosRESUMEN
OBJECTIVE: Increasing reports suggest a role for immunological mechanisms in febrile infection-related epilepsy syndrome (FIRES). The objective of this study was to elucidate the efficacy and safety of intrathecal dexamethasone therapy (IT-DEX). METHODS: We assessed six pediatric patients with FIRES who were administered add-on IT-DEX in the acute (n = 5) and chronic (n = 1) phases. We evaluated clinical courses and prognosis. We measured cytokines/chemokines in cerebrospinal fluid (CSF) from FIRES patients at several points, including pre- and post-IT-DEX, and compared them with control patients with chronic epilepsy (n = 12, for cytokines/chemokines) or with noninflammatory neurological disease (NIND, n = 13, for neopterin). RESULTS: Anesthesia was weaned after a median of 5.5 days from IT-DEX initiation (n = 6). There was a positive correlation between the duration from the disease onset to the introduction of IT-DEX and the length of ICU stay and the duration of mechanical ventilation. No patient experienced severe adverse events. Seizure spreading and background activities on electroencephalography were improved after IT-DEX in all patients. The levels of CXCL10, CXCL9, IFN-γ, and neopterin at pre-IT-DEX were significantly elevated compared to levels in epilepsy controls, and CXCL10 and neopterin were significantly decreased post-IT-DEX, but were still higher compared to patients with chronic epilepsy. IL-6, IL-8, and IL-1ß were significantly elevated before IT-DEX compared to epilepsy controls, though there was no significant decrease post-treatment. INTERPRETATION: IT-DEX represents a therapeutic option for patients with FIRES that could shorten the duration of the critical stage of the disease. The effect of IT-DEX on FIRES might include cytokine-independent mechanisms.
Asunto(s)
Antiinflamatorios/farmacología , Citocinas/efectos de los fármacos , Dexametasona/farmacología , Síndromes Epilépticos/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Evaluación de Resultado en la Atención de Salud , Antiinflamatorios/administración & dosificación , Niño , Preescolar , Citocinas/líquido cefalorraquídeo , Dexametasona/administración & dosificación , Electroencefalografía , Síndromes Epilépticos/líquido cefalorraquídeo , Síndromes Epilépticos/etiología , Síndromes Epilépticos/fisiopatología , Femenino , Fiebre/complicaciones , Humanos , Infecciones/complicaciones , Inflamación/líquido cefalorraquídeo , Inflamación/etiología , Inflamación/fisiopatología , Inyecciones Espinales , MasculinoRESUMEN
The term "developmental and epileptic encephalopathy" (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood. In this setting, neurocognition, whilst not improved by seizure control, may benefit from some precision therapies. In patients with non-progressive diseases with cognitive impairment and co-existing epilepsy, in whom the epileptiform activity does not affect or has minimal effect on function, the term "developmental encephalopathy" (DE) can be used. In contrast, for those patients with direct impact on cognition due to epileptic or epileptiform activity, the term "epileptic encephalopathy" (EE) is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Clinicians must tailor care towards individual needs and realistic expectations for each affected person; those with DE are unlikely to gain from aggressive antiseizure medication whilst those with EE will gain. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.
Asunto(s)
Síndromes Epilépticos , Trastornos Neurocognitivos , Trastornos del Neurodesarrollo , Preescolar , Síndromes Epilépticos/diagnóstico , Síndromes Epilépticos/epidemiología , Síndromes Epilépticos/etiología , Síndromes Epilépticos/terapia , Humanos , Lactante , Trastornos Neurocognitivos/diagnóstico , Trastornos Neurocognitivos/epidemiología , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/terapia , Trastornos del Neurodesarrollo/diagnóstico , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/etiología , Trastornos del Neurodesarrollo/terapiaRESUMEN
OBJECTIVE: To study the epilepsy syndromes among the severe epilepsies of infancy and assess their incidence, etiologies, and outcomes. METHODS: A population-based cohort study was undertaken of severe epilepsies with onset before age 18 months in Victoria, Australia. Two epileptologists reviewed clinical features, seizure videos, and electroencephalograms to diagnose International League Against Epilepsy epilepsy syndromes. Incidence, etiologies, and outcomes at age 2 years were determined. RESULTS: Seventy-three of 114 (64%) infants fulfilled diagnostic criteria for epilepsy syndromes at presentation, and 16 (14%) had "variants" of epilepsy syndromes in which there was one missing or different feature, or where all classical features had not yet emerged. West syndrome (WS) and "WS-like" epilepsy (infantile spasms without hypsarrhythmia or modified hypsarrhythmia) were the most common syndromes, with a combined incidence of 32.7/100 000 live births/year. The incidence of epilepsy of infancy with migrating focal seizures (EIMFS) was 4.5/100 000 and of early infantile epileptic encephalopathy (EIEE) was 3.6/100 000. Structural etiologies were common in "WS-like" epilepsy (100%), unifocal epilepsy (83%), and WS (39%), whereas single gene disorders predominated in EIMFS, EIEE, and Dravet syndrome. Eighteen (16%) infants died before age 2 years. Development was delayed or borderline in 85 of 96 (89%) survivors, being severe-profound in 40 of 96 (42%). All infants with EIEE or EIMFS had severe-profound delay or were deceased, but only 19 of 64 (30%) infants with WS, "WS-like," or "unifocal epilepsy" had severe-profound delay, and only two of 64 (3%) were deceased. SIGNIFICANCE: Three quarters of severe epilepsies of infancy could be assigned an epilepsy syndrome or "variant syndrome" at presentation. In this era of genomic testing and advanced brain imaging, diagnosing epilepsy syndromes at presentation remains clinically useful for guiding etiologic investigation, initial treatment, and prognostication.
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Discapacidades del Desarrollo/epidemiología , Epilepsias Mioclónicas/epidemiología , Espasmos Infantiles/epidemiología , Anticonvulsivantes/uso terapéutico , Preescolar , Estudios de Cohortes , Discapacidades del Desarrollo/etiología , Discapacidades del Desarrollo/fisiopatología , Progresión de la Enfermedad , Electroencefalografía , Epilepsias Mioclónicas/tratamiento farmacológico , Epilepsias Mioclónicas/etiología , Epilepsias Mioclónicas/fisiopatología , Síndromes Epilépticos/tratamiento farmacológico , Síndromes Epilépticos/epidemiología , Síndromes Epilépticos/etiología , Síndromes Epilépticos/fisiopatología , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Síndrome de Lennox-Gastaut/tratamiento farmacológico , Síndrome de Lennox-Gastaut/epidemiología , Síndrome de Lennox-Gastaut/etiología , Síndrome de Lennox-Gastaut/fisiopatología , Masculino , Malformaciones del Desarrollo Cortical/complicaciones , Malformaciones del Desarrollo Cortical/epidemiología , Malformaciones del Desarrollo Cortical/cirugía , Mortalidad , Índice de Severidad de la Enfermedad , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/etiología , Espasmos Infantiles/fisiopatología , Victoria/epidemiologíaAsunto(s)
Antirreumáticos/farmacología , Epilepsia Refractaria/tratamiento farmacológico , Síndromes Epilépticos/tratamiento farmacológico , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Estado Epiléptico/tratamiento farmacológico , Antirreumáticos/administración & dosificación , Niño , Epilepsia Refractaria/diagnóstico , Electroencefalografía , Síndromes Epilépticos/diagnóstico , Síndromes Epilépticos/etiología , Femenino , Fiebre/complicaciones , Humanos , Infecciones/complicaciones , Proteína Antagonista del Receptor de Interleucina 1/administración & dosificación , Estado Epiléptico/diagnósticoRESUMEN
We describe the efficacy of high-dose barbiturates and early administration of a parenteral ketogenic diet (KD) as initial treatments for acute status epilepticus (SE) in an 8-year-old girl with febrile infection-related epilepsy syndrome (FIRES). The patient was admitted to our hospital with refractory focal SE. Abundant epileptic discharges over the left frontal region were observed on electroencephalogram (EEG). Treatment with continuous infusion of thiamylal for 4 hours, increased incrementally to 40 mg/kg/h, successfully ended the clinical SE, and induced a burst-suppression coma. The infusion rate was then gradually decreased to 4 mg/kg/h over the next 12 hours. Parenteral KD was administered from days 6 to 21 of illness. Continuous infusion of thiamylal was switched to midazolam on day 10 without causing seizures or EEG exacerbations. The patient has remained seizure free in the 15 months since hospital discharge. The effectiveness of KD for the treatment of FIRES has attracted attention amongst clinicians, but KD treatment may need to last for 2 to 4 days before it can stop SE, a time period that could cause irreversible brain damage. Considering the severity of SE in our patient and the dose of barbiturates needed to treat it, we consider this case to have had a good clinical outcome. The results suggest that rapid termination of seizure using high-dose barbiturates in conjunction with early administration of parenteral KD could reduce the development of chronic epilepsy in patients with FIRES.
Asunto(s)
Barbitúricos/administración & dosificación , Dieta Cetogénica , Síndromes Epilépticos , Estado Epiléptico , Niño , Terapia Combinada , Electroencefalografía , Síndromes Epilépticos/dietoterapia , Síndromes Epilépticos/tratamiento farmacológico , Síndromes Epilépticos/etiología , Femenino , Fiebre/complicaciones , Humanos , Infecciones/complicaciones , Midazolam/administración & dosificación , Nutrición Parenteral , Estado Epiléptico/dietoterapia , Estado Epiléptico/tratamiento farmacológico , Estado Epiléptico/etiología , Tiamilal/administración & dosificaciónRESUMEN
Encephalitis refers to inflammation of the brain parenchyma. It is potentially life-threatening with the highest incidence and severity in younger children. Febrile infection-related epilepsy syndrome (FIRES) is a condition, in which a child develops a nonspecific febrile illness that may not persist when the initial seizure activity begins. However, an electroencephalogram (EEG) shows that the child is in status epilepticus. We report the case of a five-year-old male who presented with difficulty to maintain sitting posture, and inability to stand and walk without support, following viral encephalitis at the age of one year. He had motor, visual, speech and cognitive impairment along with a seizure disorder. The physiotherapy interventions including neurodevelopmental treatment (NDT) and sensory integration (SI) helped in regaining locomotion ability in the child. The study aims to assess the impact of physiotherapy interventions on regaining locomotor ability in a child with FIRES following infective encephalitis.
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Encefalitis/terapia , Síndromes Epilépticos/terapia , Modalidades de Fisioterapia , Convulsiones Febriles/terapia , Enfermedad Aguda , Preescolar , Electroencefalografía , Encefalitis/complicaciones , Síndromes Epilépticos/etiología , Humanos , Locomoción/fisiología , Masculino , Estado Epiléptico/etiología , Estado Epiléptico/terapia , Síndrome , Resultado del TratamientoRESUMEN
Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy characterized by new-onset refractory status epilepticus with a prior febrile infection. We performed exome sequencing in 50 individuals with FIRES, including 27 patient-parent trios and 23 single probands, none of whom had pathogenic variants in established genes for epilepsies or neurodevelopmental disorders. We also performed HLA sequencing in 29 individuals with FIRES and 529 controls, which failed to identify prominent HLA alleles. The genetic architecture of FIRES is substantially different from other developmental and epileptic encephalopathies, and the underlying etiology remains elusive, requiring novel approaches to identify the underlying causative factors.
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Enfermedades Transmisibles/complicaciones , Síndromes Epilépticos/etiología , Síndromes Epilépticos/genética , Fiebre/complicaciones , Antígenos HLA/genética , Análisis de Secuencia de ADN , Adolescente , Niño , Preescolar , Epilepsia Refractaria/etiología , Epilepsia Refractaria/genética , Femenino , Humanos , Masculino , Estado Epiléptico/etiología , Estado Epiléptico/genética , Secuenciación del ExomaRESUMEN
New-onset refractory status epilepticus (NORSE) and febrile infection-related epilepsy syndrome (FIRES) are relatively rare clinical presentations. They are characterized by de novo onset of refractory status epilepticus (RSE) without clearly identifiable acute or active cause (structural, toxic, or metabolic). We reviewed the literature using PubMed reports published between 2003 and 2019 and summarized the clinical, neurophysiological, imaging, and treatment findings. Focal motor seizures, which tend to evolve into status epilepticus, characterize the typical presentation. Disease course is biphasic: acute phase followed by chronic phase with refractory epilepsy and neurological impairment. Aetiology is unknown, but immune-inflammatory-mediated epileptic encephalopathy is suspected. Electroencephalograms show variety in discharges (sporadic or periodic, focal, generalized, or more frequently bilateral), sometimes with a multifocal pattern. About 70% of adult NORSE have abnormal magnetic resonance imaging (MRI); in paediatric series of FIRES, 61.2% of patients have a normal brain MRI at the beginning and only 18.5% during the chronic phase. No specific therapy for FIRES and NORSE currently exists; high doses of barbiturates and ketogenic diet can be used with some effectiveness. Recently, anakinra and tocilizumab, targeting interleukin pathways, have emerged as potential specific therapies. Mortality rate is around 12% in children and even higher in adults (16-27%).
Asunto(s)
Síndromes Epilépticos/fisiopatología , Fiebre/complicaciones , Infecciones/complicaciones , Estado Epiléptico/fisiopatología , Síndromes Epilépticos/diagnóstico , Síndromes Epilépticos/etiología , Humanos , Estado Epiléptico/complicaciones , Estado Epiléptico/diagnósticoRESUMEN
BACKGROUND: Febrile infection-related epilepsy syndrome is associated with high mortality and morbidity rates. No systematic review of demographics, aetiologies, good treatment options, and causes of deaths has been performed. Thus, we aimed to focus on these factors to provide a structure for patient management and research. METHODS: A deep literature search was performed in PubMed and Embase of all years until May 2019. RESULTS: We retrieved 45 aSrticles: 3 multicentre cohort studies, 13 single-centre cohorts, 1 case series, and 28 case reports. We identified 229 cases: most were from Asia; 53% were males; 11.4% had several types of antibodies, and the most common was anti-glutamate receptor epsilon 2; 30% (69 cases) had good treatment outcomes; 12.2% died; and 56% remained with drug-resistant epilepsies. Univariate analysis revealed a statistically significant association between positive outcomes in Japan and China, the use of the ketogenic diet either acutely or chronically, and the use of steroids acutely or chronically. Taiwan showed a statistically significant association with negative outcomes. Multivariate logistic regression revealed the utilisation of the ketogenic diet in the acute phases (P = 0.008, OR = 3.613) and being in Japan (P = 0.003, OR = 3.146) as independent determinants of positive outcomes. Most of the deaths occurred because of the progress of the disease rather than complications of the drugs. CONCLUSIONS: Asians are more affected and several cases have antibodies. Positive outcomes are associated with being in Japan and the utilisation of the ketogenic diet in the acute phase.
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Enfermedad Aguda , Enfermedad Crónica , Síndromes Epilépticos , Infecciones , Convulsiones Febriles , Enfermedad Aguda/epidemiología , Enfermedad Aguda/terapia , Enfermedad Crónica/epidemiología , Enfermedad Crónica/terapia , Síndromes Epilépticos/epidemiología , Síndromes Epilépticos/etiología , Síndromes Epilépticos/inmunología , Síndromes Epilépticos/terapia , Humanos , Infecciones/complicaciones , Infecciones/epidemiología , Convulsiones Febriles/epidemiología , Convulsiones Febriles/etiología , Convulsiones Febriles/inmunología , Convulsiones Febriles/terapiaRESUMEN
Febrile infection-related epilepsy syndrome (FIRES) is an intractable neurological disease characterized by an unexplained refractory status epilepticus triggered by febrile infection. A Consensus definition of FIRES was proposed in 2018, and its clinical features and prognosis are gradually being clarified. However, the development of effective treatments has been hindered as the etiology of this rare disease is as yet unelucidated. The basic approach to the management of FIRES, like other forms of epilepsy, is based on the control of seizures, however seizures are extremely intractable and require intravenous administration of large doses of anticonvulsants, mainly barbiturates. This treatment strategy produces various complications including respiratory depression and drug hypersensitivity syndrome, which make it more difficult to control seizures. Consequently, it is crucial to predict these events and to formulate a planned treatment strategy. As well, it is important to grow out of conventional treatment strategies that rely on only anticonvulsants, and alternative therapies are gradually being developed. One such example is the adoption of a ketogenic diet which may lead to reduced convulsions as well as improve intellectual prognosis. Further, overproduction of inflammatory cytokines in the central nervous system has been shown to be strongly related to the pathology of FIRES which has led to attempts at immunomodulation therapy including anti-cytokine therapy.
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Síndromes Epilépticos , Fiebre/etiología , Infecciones/complicaciones , Anticonvulsivantes/uso terapéutico , Síndromes Epilépticos/etiología , Síndromes Epilépticos/terapia , Humanos , Inmunoterapia , Convulsiones/tratamiento farmacológicoRESUMEN
Febrile infection-related epilepsy syndrome (FIRES) is a rare and devastating epileptic encephalopathy with historically abysmal neurocognitive outcomes, including a high incidence of mortality. It tends to affect children and young adults and is characterized by superrefractory status epilepticus following a recent febrile illness. Growing evidence suggests a heterogeneous etiology resulting in fulminant nonantibody-mediated neuroinflammation. For some children with FIRES, this aberrant neuroinflammation appears secondary to a functional deficiency in the endogenous interleukin-1 receptor antagonist. A precise etiology has not been identified in all FIRES patients, and current treatments are not always successful. Limited treatment evidence exists to guide choice, dosing, and duration of therapies. However, the ketogenic diet and certain targeted immunomodulatory treatments, including anakinra, appear safe and have been associated with relatively excellent clinical outcomes in some FIRES patients. Future prospective multicenter collaborative studies are needed to further delineate the FIRES heterogeneous disease pathophysiology and to determine the safety and efficacy of treatment strategies through a robust measurement of neurocognitive outcomes.
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Enfermedades Transmisibles/complicaciones , Epilepsia Refractaria/terapia , Síndromes Epilépticos/terapia , Fiebre/complicaciones , Inflamación/terapia , Estado Epiléptico/terapia , Epilepsia Refractaria/etiología , Epilepsia Refractaria/inmunología , Síndromes Epilépticos/etiología , Síndromes Epilépticos/inmunología , Humanos , Inflamación/etiología , Inflamación/inmunología , Estado Epiléptico/etiología , Estado Epiléptico/inmunologíaRESUMEN
BACKGROUND: In the presence of a skull deformity after large decompressive craniectomy (DC), neurologic deterioration manifesting as epileptic syndrome (ES) may occur independently of the primary disease or spontaneous improvement may be unduly impaired, and these unfavorable outcomes have sometimes been reversed by cranioplasty. The objective of this study was to analyze the influence of cranioplasty on the presence of ES in patients who underwent DC. METHODS: A prospective study was performed from October 2016 to October 2017 involving patients who underwent DC and subsequent cranioplasty. Electroencephalographic (EEG) status before and after cranioplasty was analyzed in the presence of seizures and was compared with results after DC. RESULTS: The sample included 52 patients. Male sex (78.8%) and traumatic brain injury (82.7%) were common indications for DC. ES after DC was verified in 26.9% of patients, and 50% of patients presented with abnormal EEG status. ES after cranioplasty was noted in 21.2% and 36.3% of patients followed by abnormal EEG status. All patients with precranioplasty epileptogenic paroxysms showed better EEG tracings after the procedure. CONCLUSIONS: In routine clinical practice, altered amplitudes were observed in the region of bone defects. Although cranioplasty reduced pathologic EEG status (epileptogenic paroxysms), it was not able to produce new EEG tracings that could predict changes in seizure discharge or reduce ES.
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Craniectomía Descompresiva/efectos adversos , Síndromes Epilépticos/cirugía , Complicaciones Posoperatorias/cirugía , Convulsiones/cirugía , Cráneo/cirugía , Adulto , Lesiones Traumáticas del Encéfalo/cirugía , Electroencefalografía , Síndromes Epilépticos/etiología , Síndromes Epilépticos/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Defectos del Tubo Neural , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/fisiopatología , Estudios Prospectivos , Procedimientos de Cirugía Plástica , Convulsiones/etiología , Convulsiones/fisiopatología , Resultado del Tratamiento , Adulto JovenRESUMEN
Developmental and Epileptic encephalopathies (DEE) describe heterogeneous epilepsy syndromes, characterized by early-onset, refractory seizures and developmental delay (DD). Several DEE associated genes have been reported. With increased access to whole exome sequencing (WES), new candidate genes are being identified although there are fewer large cohort papers describing the clinical phenotype in such patients. We describe 6 unreported individuals and provide updated information on an additional previously reported individual with heterozygous de novo missense variants in YWHAG. We describe a syndromal phenotype, report 5 novel, and a recurrent p.Arg132Cys YWHAG variant and compare developmental trajectory and treatment strategies in this cohort. We provide further evidence of causality in YWHAG variants. WES was performed in five patients via Deciphering Developmental Disorders Study and the remaining two were identified via Genematcher and AnnEX databases. De novo variants identified from exome data were validated using Sanger sequencing. Seven out of seven patients in the cohort have de novo, heterozygous missense variants in YWHAG including 2/7 patients with a recurrent c.394C > T, p.Arg132Cys variant; 1/7 has a second, pathogenic variant in STAG1. Characteristic features included: early-onset seizures, predominantly generalized tonic-clonic and absence type (7/7) with good response to standard anti-epileptic medications; moderate DD; Intellectual Disability (ID) (5/7) and Autism Spectrum Disorder (3/7). De novo YWHAG missense variants cause EE, characterized by early-onset epilepsy, ID and DD, supporting the hypothesis that YWHAG loss-of-function causes a neurological phenotype. Although the exact mechanism of disease resulting from alterations in YWHAG is not fully known, it is possible that haploinsufficiency of YWHAG in developing cerebral cortex may lead to abnormal neuronal migration resulting in DEE.
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Proteínas 14-3-3/genética , Síndromes Epilépticos/etiología , Estudios de Asociación Genética , Heterocigoto , Mutación Missense , Trastornos del Neurodesarrollo/etiología , Adolescente , Niño , Preescolar , Síndromes Epilépticos/patología , Femenino , Humanos , Masculino , Trastornos del Neurodesarrollo/patologíaRESUMEN
Rett syndrome (RTT) and CDKL5 deficiency disorder (CDD) are two rare X-linked developmental brain disorders with overlapping but distinct phenotypic features. This review examines the impact of loss of methyl-CpG-binding protein 2 (MeCP2) and cyclin-dependent kinase-like 5 (CDKL5) on clinical phenotype, deficits in synaptic- and circuit-homeostatic mechanisms, seizures, and sleep. In particular, we compare the overlapping and contrasting features between RTT and CDD in clinic and in preclinical studies. Finally, we discuss lessons learned from recent clinical trials while reviewing the findings from pre-clinical studies.
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Síndromes Epilépticos/diagnóstico , Síndromes Epilépticos/etiología , Síndromes Epilépticos/terapia , Síndrome de Rett/diagnóstico , Síndrome de Rett/etiología , Síndrome de Rett/terapia , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/etiología , Espasmos Infantiles/terapia , Animales , Ensayos Clínicos como Asunto , Diagnóstico Diferencial , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Proteína 2 de Unión a Metil-CpG/genética , Proteína 2 de Unión a Metil-CpG/metabolismo , Mutación , Evaluación de Resultado en la Atención de Salud , Fenotipo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Investigación Biomédica TraslacionalRESUMEN
PURPOSE: This study aimed to identify disease-causing gene mutations in individuals belonging to the Southern Chinese Han population diagnosed with fever-associated seizures or epilepsy (FASE). METHODS: Blood samples and clinical data were collected from 78 children with FASE. All subjects were screened for mutations using whole-exome sequencing, and mutations were validated using the Sanger sequencing method. RESULTS: Three novelSCN9A heterozygous missense mutations (I775M, R429C and A442T) were noted, which are associated with febrile seizures (FS), febrile seizures plus (FS+) and genetic epilepsy with febrile seizures plus (GEFS+), respectively. The R429C and A442T mutations are located in the large cytoplasmic loop between transmembrane topological domains, whereas I775M is located in the topological domain DIIS2. The I775M and R429C mutations have highly evolutionarily conserved residues and are predicted to affect the SCN9A protein function according to bioinformatics tools. These three mutations were not identified in 300 unrelated control subjects. CONCLUSIONS: Mutations in theSCN9A gene may be linked with FASE.
Asunto(s)
Síndromes Epilépticos/genética , Canal de Sodio Activado por Voltaje NAV1.7/genética , Convulsiones Febriles/genética , Niño , Preescolar , Síndromes Epilépticos/etiología , Femenino , Fiebre/complicaciones , Humanos , Masculino , Mutación , Secuenciación del ExomaRESUMEN
Febrile infection-related epilepsy syndrome (FIRES) is a rare severe epileptic syndrome occurring in previously healthy children and characterized by refractory status epilepticus (SE) following a febrile illness. Brain imaging findings in affected patients have been reported in few case series and some case reports. This article is a comprehensive review of the magnetic resonance imaging (MRI) characteristics in all reported patients with a diagnosis of FIRES, describing the findings in the acute and chronic phases of the disease, and discussing possible pathogenesis and radiologic differential diagnoses. Most of the patients had normal brain scans in the acute phase (61%) and about 25% of the patients reported in literature had abnormalities in the temporal lobes. Changes in the basal ganglia and rarely in thalami or brainstem have also been described, as well as diffuse cerebral edema in a minority of patients during the acute phase. The chronic phase of the disease was characterized by atrophic changes and evidence of mesiotemporal sclerosis. An understanding of these MRI abnormalities is necessary to support the diagnosis of FIRES and exclude mimics.
Asunto(s)
Epilepsia Refractaria/diagnóstico por imagen , Síndromes Epilépticos/diagnóstico por imagen , Neuroimagen/métodos , Convulsiones Febriles/diagnóstico por imagen , Estado Epiléptico/diagnóstico por imagen , Niño , Preescolar , Epilepsia Refractaria/etiología , Epilepsia Refractaria/patología , Síndromes Epilépticos/etiología , Síndromes Epilépticos/patología , Femenino , Humanos , Infecciones/complicaciones , Masculino , Convulsiones Febriles/patología , Estado Epiléptico/etiología , Estado Epiléptico/patologíaRESUMEN
Neonatal convulsions are the most frequent form of expression of neurological pathology in the neonatal period. They represent a neurological emergency and thus require urgent diagnosis and treatment, as they are associated with a high risk of neonatal mortality or adverse neurological prognosis. Most neonatal convulsions are symptomatic and secondary to an identifiable causation. The causes vary widely. In this review we describe the electroclinical and aetiological aspects, and we also analyse the process of diagnosing the main epileptic syndromes in newborn infants. The importance of their diagnosis is due to the fact that some disorders are amenable to specific treatments, as in the case of some channelopathies or inborn errors of metabolism that are sensitive to vitamins. Early diagnosis and treatment are therefore essential to prevent a catastrophic outcome.
TITLE: Sindromes epilepticos de inicio neonatal. Etiologias y proceso diagnostico.Las convulsiones neonatales constituyen la forma de expresion mas frecuente de patologia neurologica en el periodo neonatal. Son una emergencia neurologica y por ello requieren un diagnostico y tratamiento urgente, puesto que asocian un riesgo elevado de mortalidad neonatal o de pronostico neurologico adverso. La mayoria de las convulsiones neonatales son sintomaticas y secundarias a una etiologia identificable. Las causas son muy heterogeneas. En esta revision describiremos los aspectos electroclinicos y etiologicos, y analizaremos el proceso diagnostico de los principales sindromes epilepticos del recien nacido. La importancia de su diagnostico se debe a que algunos trastornos son susceptibles de tratamientos especificos, como el caso de algunas canalopatias o los errores congenitos del metabolismo sensibles a vitaminas, por lo que el diagnostico y el tratamiento precoz son fundamentales para evitar una evolucion catastrofica.
Asunto(s)
Síndromes Epilépticos/diagnóstico , Síndromes Epilépticos/etiología , Edad de Inicio , Humanos , Recién NacidoRESUMEN
BACKGROUND: KANSL1 haploinsufficiency causes Koolen-de Vries syndrome (KdVS), characterized by dysmorphic features and intellectual disability; amiable personality, congenital malformations and seizures also commonly occur. The epilepsy phenotypic spectrum in KdVS is broad, but most individuals have focal seizures with some having a phenotype resembling the self-limited focal epilepsies of childhood (SFEC). We hypothesized that variants in KANSL1 contribute to pathogenesis of SFEC. MATERIALS AND METHODS: We screened KANSL1 for single nucleotide variants in 90 patients with SFEC. We then screened a cohort of 208 patients with two specific SFEC syndromes, childhood epilepsy with centrotemporal spikes (CECTS) and atypical childhood epilepsy with centrotemporal spikes (ACECTS) for KANSL1 variants. The second cohort was also used to evaluate minor allelic variants that appeared overrepresented in the initial cohort. RESULTS: One variant, p.Lys104Thr, was predicted damaging and appeared overrepresented in our 90-patient cohort compared to Genome Aggregation Database (gnomAD) allele frequency (0.217 to 0.116, with no homozygotes in gnomAD). However, there was no difference in p.Lys104Thr allele frequency in the follow-up CECTS/ACECTS cohort and controls. Four rare KANSL1 variants of uncertain significance were identified in the CECTS/ACECTS cohort. DISCUSSION: Our data do not support a major role for KANSL1 variants in pathogenesis of SFEC.
Asunto(s)
Síndromes Epilépticos/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleótido Simple , Anomalías Múltiples/genética , Sustitución de Aminoácidos , Niño , Deleción Cromosómica , Cromosomas Humanos Par 17/genética , Estudios de Cohortes , Bases de Datos Genéticas , Epilepsias Parciales/genética , Epilepsia Rolándica/genética , Síndromes Epilépticos/etiología , Frecuencia de los Genes , Variación Genética , Humanos , Discapacidad Intelectual/genéticaRESUMEN
According to the International League Against Epilepsy's (ILAE) Commission on Classification and Terminology, the term 'epileptic encephalopathy' reflects the notion that epileptic activity in itself can contribute to the genesis of severe cognitive or behavioural disabilities, beyond what could be expected from the pathology underlying the epilepsy. However, in many cases it is difficult to define the boundary between the relative contribution of the epileptic seizures and the underlying cause in the genesis of cognitive deficits. Some epileptic syndromes, such as those of West, Lennox-Gastaut or Dravet, are associated to a high probability of encephalopathic traits. The most frequent causes of epileptic encephalopathy are hypoxic-ischaemic encephalopathy, brain malformations, including cortical dysplasias, chromosomal or genetic disorders, tuberous sclerosis and metabolic diseases.
TITLE: Encefalopatias epilepticas.Segun la Comision de Clasificacion y Terminologia de la Liga Internacional contra la Epilepsia (ILAE), el termino 'encefalopatia epileptica' refleja la nocion de que la actividad epileptica en si misma puede contribuir a la genesis de graves discapacidades cognitivas o comportamentales, mas alla de lo que seria de esperar de la patologia subyacente a la epilepsia. No obstante, en muchos casos resulta dificil deslindar la contribucion relativa de las crisis epilepticas y la causa subyacente en la genesis de los deficits cognitivos. Algunos sindromes epilepticos, como los de West, Lennox-Gastaut o Dravet, se asocian con una alta probabilidad de rasgos encefalopaticos. Las causas mas frecuentes de encefalopatia epileptica son la encefalopatia hipoxico-isquemica, las malformaciones cerebrales, incluyendo las displasias corticales, las alteraciones cromosomicas o geneticas, la esclerosis tuberosa y las enfermedades metabolicas.